title: MicroRNA-141-3p plays a role in human mesenchymal stem cell aging by directly targeting ZMPSTE24.
abstract: Human mesenchymal stem cell (hMSC) aging may lead to a reduced tissue regeneration capacity and a decline in physiological functions. However, the molecular mechanisms controlling hMSC aging in the context of prelamin A accumulation are not completely understood. In this study, we demonstrate that the accumulation of prelamin A in the nuclear envelope results in cellular senescence and potential downstream regulatory mechanisms responsible for prelamin A accumulation in hMSCs. We show for the first time that ZMPSTE24, which is involved in the post-translational maturation of lamin A, is largely responsible for the prelamin A accumulation related to cellular senescence in hMSCs. Direct binding of miR-141-3p to the 3'UTR of ZMPSTE24 transcripts was confirmed using a 3'UTR-luciferase reporter assay. We also found that miR-141-3p, which is overexpressed during senescence as a result of epigenetic regulation, is able to decrease ZMPSTE24 expression levels, and leads to an upregulation of prelamin A in hMSCs. This study provides new insights into mechanisms regulating MSC aging and may have implications for therapeutic application to reduce age-associated MSC pool exhaustion.
authors.affiliation: Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Kyung-Rok
authors.initials: KR
authors.lastname: Yu
authors.forename: Seunghee
authors.initials: S
authors.lastname: Lee
authors.forename: Ji-Won
authors.initials: JW
authors.lastname: Jung
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Hong
authors.forename: Hyung-Sik
authors.initials: HS
authors.lastname: Kim
authors.forename: Yoojin
authors.initials: Y
authors.lastname: Seo
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Shin
authors.forename: Kyung-Sun
authors.initials: KS
authors.lastname: Kang
mesh_terms: D020413:3' Untranslated Regions; D016922:Cellular Senescence / Q000235:genetics; D044127:Epigenesis, Genetic; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D034904:Lamin Type A; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D061251:Primary Cell Culture; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; D034904:Lamin Type A; C533895:MIRN141 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A; D008156:Luciferases; D008666:Metalloendopeptidases; C120130:ZMPSTE24 protein, human
keywords: Aging; Histone modification; Mesenchymal stem cells; Prelamin A accumulation; ZMPSTE24; miRNA-141-3p